Identification and Validation of Key Genes Related to Arginine Methylation Modification in Sepsis Using Transcriptome Combined with Mendelian Randomization Analysis.

BACKGROUND: Patients with sepsis often exhibit a decrease in lymphatic numbers, which can be facilitated by protein arginine methyltransferase (PRMT). However, it is unclear how PRMT contributes to lymphopenia in sepsis. METHODS: This study employed the sepsis-related datasets (GSE65682 and GSE134347) and nine PRMT genes. First, we intersected the differentially expressed genes with the weighted gene co-expression network analysis module genes to identify differentially expressed PRMT-related genes. Thereafter, candidate key genes were obtained after Mendelian randomization analysis and machine learning screening. Eventually, we subjected key genes identified by expression analysis and receiver operating characteristic curves to gene set enrichment analysis, immune infiltration analysis, immune checkpoint analysis, molecular docking, regulatory networks construction, and nomogram development. RESULTS: We first intersected 4,246 differentially expressed genes with 1,884 PRMT scoring module genes to obtain 969 differentially expressed PRMT-related genes. Further Mendelian randomization analysis and machine learning jointly identified five candidate genes ( CRLF3 , ELAC2 , PBX2 , MCTP2 , and EMB ). Among these, ELAC2 , PBX2 , MCTP2 , and EMB demonstrated consistent expression trends, with the area under the curve values of the receiver operating characteristic curve exceeding 0.7 in GSE65682 and GSE134347. Therefore, they were defined as key PRMT-related genes. The gene set enrichment analysis showed enrichment in cytoplasmic translation ( ELAC2 , MCTP2 ), noncoding RNA metabolism ( EMB ), and metabolic processes ( PBX2 ). The immune infiltration analysis revealed a significant correlation between PBX2 and neutrophils, as well as between ELAC2 / MCTP2 / EMB with activated natural killer cells, CD8+ T cells. CONCLUSION: In this study, ELAC2 , PBX2 , MCTP2 , and EMB were identified as key genes related to PRMT for sepsis, which provided a theoretical basis for the study of sepsis.